Robert Glenn Quivey, Jr., Ph.D.

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Our research work is focused on a bacterium, Streptococcus mutans, which colonizes the human mouth from the time of tooth eruption until death. The persistence of the organism is remarkable and our efforts are directed to learning the biological means by which it chronically infects virtually every person in the developed nations. The infection requires two relatively simple-minded objectives: bind to tooth surfaces and then survive in the mouth. However, the mouth is a fairly inhospitable environment, containing between 400 and 500 competing bacterial species, volumes of saliva that are swallowed, desquamating soft tissue surfaces, and the swallowing of food (and adsorbed bacteria) as a bolus. Irreversible binding of tooth surfaces occurs by the action of extracellular enzymes produced by S. mutans, the glucosyltransferases (GTFs). These enzymes catalyze the conversion of sucrose, supplied in our diets, to long-chain, insoluble glucans that serve as the molecular scaffold for the formation of dental plaque. If not removed, physically from teeth, the growing mesh of glucan, food particles, bacteria, and salivary constituents continues to accumulate and forms a biofilm referred to as dental plaque. As plaque builds up, S. mutans becomes protected from the flushing effects of saliva and swallowing. In its protected niche, S. mutans metabolism of sugar results in the formation of organic acids and the rapid acidification of the surrounding milieu. As pH values plummet, several orders of magnitude in just seconds, S. mutans begins its adaptation to life at low pH values, where surrounding bacteria can not compete. Our work is in understanding the mechanisms of low pH adaptation and how it relates to bacterial virulence in biofilms.

Results from our efforts have shown that S. mutans utilizes a number of discrete mechanisms to survive acidic environments. Interestingly, we've found that some of the mechanisms are shared with other streptococcal pathogens, and some are shared with streptococcal and staphylococcal pathogens. For example, we've shown that the central acid-protective enzyme, the F-ATPase, is transcriptionally up-regulated ("on") at low pH, which is characteristic shared with S. pneumoniae (Kuhnert et al., 2004). Our data has also shown that S. mutans must make major alterations to its membrane to survive low pH, requiring the action of an enzyme called FabM, a condition that is apparently shared in Staphylococcus aureus (Fozo and Quivey, 2004). Further evidence from our group has shown that resistance to acid-stress overlaps stress from oxidative agents, such as hydrogen peroxide, and that control of oxygen metabolism by an enzyme called NADH oxidase is mediated, in part, by novel mechanisms unique to S. mutans (Karrupaiah et al., 2005). In all of this work, we have focused on identifying those elements that might be useful targets for therapeutic intervention. Our results have shown that identification of unique regulatory schemes or novel enzyme mechanisms involved in stress responses in S. mutans also have a possible usefulness in other human pathogens. We are pursuing or basic science goals, with the inclusion of translational work. For example, we are exploring the use of metal ions, with knowledge gained from DNA repair studies, to develop new therapies for bacterial infection (Faustoferri et al., 2005). We have also begun the use of transgenic mice to study early infection processes (Culp et al., 2005). And, finally, we are developing new technology, in conjunction with the Optics Institute, to rapidly determine the bacterial composition of clinical biofilm samples (Zhu et al., 2004).

Current Appointments

• Director - Center for Oral Biology (SMD)
• Dean's Professorship - Department of Dean's Office, SMD (SMD)
• Professor - Department of Microbiology and Immunology, Center for Oral Biology (SMD)

Lab Description

Bacterial Physiology and Genetics; Molecular Biology of Acid-Adaptation in Streptococcus mutans, an Oral Pathogen.